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Case Reports
. 2020 Sep 2;12(3):319-328.
doi: 10.4274/jcrpe.galenos.2019.2019.0142. Epub 2019 Nov 29.

Ectopic Posterior Pituitary, Polydactyly, Midfacial Hypoplasia and Multiple Pituitary Hormone Deficiency due to a Novel Heterozygous IVS11-2A>C(c.1957-2A>C) Mutation in the GLI2 Gene

Meliha Demiral  1 , Hüseyin Demirbilek  2 , Edip Unal  1 , Ceren Damla Durmaz  3 , Serdar Ceylaner  4 , Mehmet Nuri Özbek  1
Affiliations
Case Reports

Ectopic Posterior Pituitary, Polydactyly, Midfacial Hypoplasia and Multiple Pituitary Hormone Deficiency due to a Novel Heterozygous IVS11-2A>C(c.1957-2A>C) Mutation in the GLI2 Gene

Meliha Demiral et al. J Clin Res Pediatr Endocrinol. .

Abstract

A novel heterozygous IVS11-2A>C(c.1957-2A>C) mutation in the GLI2 gene is reported. There was an extremely distinct phenotypical expression in two siblings and their father. The index case was a boy who developed cholestasis and hypoglycaemia in the neonatal period. He had bilateral postaxial polydactyly, mid-facial hypoplasia, high palatal arch, micropenis, and bilateral cryptorchidism. Laboratory examination revealed a diagnosis of multiple pituitary hormone deficiency. There was severe anterior pituitary hypoplasia, absent pituitary stalk and ectopic posterior pituitary on magnetic resonance imaging which suggested pituitary stalk interruption syndrome with no other midline structural abnormality. Molecular genetic analysis revealed a novel heterozygous splicing IVS11-2A>C(c.1957-2A>C) mutation detected in the GLI2 gene. His father and a six-year-old brother with the identical mutation also had unilateral postaxial polydactyly and mid-facial hypoplasia although there was no pituitary hormone deficiency. This novel heterozygous GLI2 mutation detected appears to present with an extremely variable clinical phenotype, even in related individuals with an identical mutation, suggesting incomplete penetrance of this GLI2 mutation.

Keywords: Growth hormone deficiency; polydactyly; GLI2 mutations; multiple pituitary hormone deficiency.

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Figures

Figure 1
Figure 1
Facial dysmorphism and polydactyly in the index case, brother and father (a-f). Good response to recombinant human growth hormone therapy in the index case (g)
Figure 2
Figure 2
Family pedigree and electropherogram of heterozygous IVS11-2A>C(c.1957-2A>C) mutation in the GLI2 gene. Full-black filled box indicates index case with Culler-Jones syndrome phenotype, shaded boxes indicate father and brother who are also heterozygous for the identical mutation with incomplete phenotype, empty boxes indicate mother and sister with wild type
See this image and copyright information in PMC

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